To estimate the normal ageing effect, the white matter of the human brain has been segmented into major fiber tracts based on the diffusion tensor imaging (DTI) data¹. Yet, no diffusion MRI study has ever investigated the detailed changes in the microstructural integrity along the commissure fibers tracts. Our hypothesis considered that the commissure fiber tracts were highly sensitive to aging. This study used template-based diffusion spectrum imaging (DSI) tractography to analyze the microstructural integrity of commissure fiber tracts based on the generalized fractional anisotropy (GFA) values. We took the GFA profiles as realizations sampled from random functions and applied functional data analysis to investigate the age effect on the tract integrity. Subjects The subjects included 63 young healthy right-handed adults and 49 healthy elderly right-handed adults. Image Acquisition MR scanning was performed on a 3T MRI system (Siemens) with a 32 channel head coil. DSI was acquired using diffusion echo planar imaging sequence, TR/TE = 9600/130ms, FOV = 200 mm, image matrix size = 80 x 80, and 2.5 mm slice thick. A total of 102 diffusion encoding gradients with the maximum diffusion sensitivity bmax = 4000 s/mm^2 were sampled on the grid points in a half sphere of the 3D q-space with |q|≤ 3.6 units. DSI template-based analytical analysis The tract-based automatic analysis (TBAA) method requires 2 pieces of information, a high quality DSI template and a whole brain white matter tract atlas². Whole brain white matter tracts were reconstructed on the DSI template using multiple regions of interest (ROIs) and whole brain seeding. A total of 18 commissure fiber tracts were reconstructed from 36 ROIs defined in the Automatic Anatomical Labeling system. Each reconstructed tract was subdivided into multiple steps with even spacing and the step coordinates along tract bundles were saved as sampling coordinates³. GFA profiles analyses We compared the GFA profiles of the 18 tracts between the young and the elderly groups by the multiple hypotheses testing evaluating both FDR and FWER⁴. Further, we developed a functional response model incorporating age as the covariate to examine the ageing effect on the GFA profiles. The fitted age-specific GFA profiles were at age 20, 30, 40 for the young group and age 60, 70, 80 for the elderly group.Fifteen out of the 18 commissure fibers were selected from the group comparisons test, the first component of which showed significant group differences (Table 1). The cross-sectional profiles of GFA values showed that 7 out of the 15 commissure fibers were highly sensitive to the aging effect (Figure 1). The age curves of the mean GFA profiles were clearly age-dependent. Among the 7 fiber tracts, the anterior commissure fibers (Genu, Dorsal Lateral Prefrontal Cortex, Ventral Lateral Prefrontal Cortex, Anterior Commissure,) displayed obvious aging patters across the lifespan (Figure 2a). The posterior commissure fibers (Posterior Commissure, CC hippocampus, CC temporal pole) showed aging effect after 60 years old (Figure 2b). This is the first study to show the aging patters of the commissure fibers. The anterior commissure fibers are highly sensitive to the aging effect across the lifespan. The poster commissure fibers become sensitive to the aging effect after 60 years old. In conclusion, our study provides specific degenerative patterns of the commissure fibers tracts in normal ageing which may serve as a useful reference for neurodegenerative diseases.